Chance Of Long-term Survival Research Articles

Conservation in human-dominated landscapes: Lessons from the distribution of the Central American squirrel monkey

It is becoming increasingly evident that many species can tolerate different degrees of habitat perturbation and that we often underestimate the capacity of some human-modified landscapes to support populations of declining species. We provide new insights into the distribution of the endangered Central American squirrel monkey and habitat changed over the last 20 years. The species has shown an approximate 60% decrease between the historic and the present extent of occurrence, with an area of occupancy of also about 60% of the present extent of occurrence. Despite the large habitat alteration, our results show surprisingly that this endangered monkey can persist in highly perturbed landscapes. This offers opportunities to improve its long-term chances of survival through conservation actions to protect and restore its habitat on the one hand, and to reduce the monkey's direct mortality on the other. Surprisingly we found several troops in 16 localities in a large area along the Rio Coto Brus where the Central American squirrel monkey was previously unrecorded. Some of our observations were made in cloud forests at a record high altitude for this species. We speculate the monkeys are using these highland areas as a corridor between suitable lowland habitats in the Coto Brus and the Rio Sierpe-Osa Peninsula regions. In response, we suggest strategies to help in the monkey's long-term conservation, that can be used as an example for other endangered species.

Survival after primary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (FFCD ACHBTH AURC 9002 trial and EORTC Intergroup trial 40983).

e15019 Background: Metastatic colorectal cancer (mCRC) patients (pts) with liver-limited disease (LLD) have a chance of long-term survival and cure after hepatic metastasectomy. The optimal treatment after primary liver resection remains controversial. Here we compare results from the LICC trial with historical controls, the FFCD ACHBTH AURC 9002 trial (FFCD; Portier et al., 2006) and the EORTC Intergroup trial 40983 (EORTC; Nordlinger et al., 2008, 2013). The three trials investigated pts with mCRC LLD who underwent primary hepatic resection. Methods: LICC, FFCD and EORTC were compared regarding pts characteristics, treatment, surveillance and efficacy outcomes. LICC pts received the adjuvant antigen-specific cancer vaccine tecemotide (L-BLP25) or placebo after primary LLD resection for up to 2 years. The FFCD trial compared postoperative 5-FU/leucovorin and the EORTC trial perioperative FOLFOX versus surgery alone. Results: Primary resected pts in LICC (n = 80; R0 n = 76), FFCD (R0 n = 171; postoperative chemotherapy n = 86) and EORTC (n = 364) showed different pt characteristics concerning median age (60, 63 and 63 years) and rate of synchronous metastases (46.8%, 27.9% and 34.0%). In LICC, > 5 liver metastases were resected in 11.6% of pts, in FFCD and EORTC all eligible pts had < 5 liver metastases resected. In contrast to EORTC, LICC and FFCD had a close surveillance until recurrence or a maximum of 2 years. Median OS (mOS) in LICC was not yet estimable in primary resected pts (tecemotide arm: 62.8 months; placebo arm: not yet estimable). In the FFCD and the EORTC trial, mOS was 62.1 and 61.3 months, respectively. Further details will be presented. Conclusions: Despite unfavorable disease characteristic in LICC compared with the earlier EORTC and FFCD studies, primary liver resection without adjuvant chemotherapy led to surprisingly good survival outcomes. Improvements in imaging-based pt selection and liver resection techniques might in part explain our finding. Surgery alone appears to be an option for selected pts with resectable LLD. Better systemic chemo(immune-)therapy may have also contributed to the OS benefit. Clinical trial information: LICC: NCT01462513; EORTC: NCT00006479; FFCD: not registered.

Survival after secondary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (CELIM, FIRE-3).

e15025 Background: Metastatic colorectal cancer (mCRC) patients (pts) with liver-limited disease (LLD) have a chance of long-term overall survival (OS) and potential cure after complete hepatic metastasectomy. The appropriate postoperative treatment strategy is still controversial. L-BLP25 as antigen-specific cancer vaccine targeting mucin 1 (MUC1) was recently evaluated as adjuvant therapy in mCRC pts after R0/R1 LLD resection (LICC trial, NCT01462513). Here we compared the LICC surveillance program and efficacy results for secondarily resected LLD pts versus historical controls, i.e. the CELIM trial (Folprecht et al, Ann Oncol 2014) of potentially resectable LLD mCRC pts and a FIRE-3-LLD subgroup (Holch et al, Int J Cancer 2018). Methods: LICC, CELIM and FIRE-3-LLD subgroup pts with stage IV mCRC limited to liver metastases who underwent hepatic resection (R0 or R1) were compared regarding pts characteristics, surveillance and efficacy outcome. LICC pts received adjuvant L-BLP25 or placebo after secondary LLD resection as 8 weekly doses, followed by 6 week maintenance intervals and tight surveillance until recurrence or a maximum of 2 years. Results: In LICC, 41 /121 pts (33.9%) were secondarily resected, and R0 resection was achieved in 31 pts (75.6%). In CELIM, 36/106 pts (34%) with primary unresectable LLD were secondarily R0 resected. In FIRE-3-LLD, secondary resection was feasible for 29/133 pts (21.8%). After R0 resection, median recurrence free survival (mRFS) was 8.9 months in LICC, 9.9 months in CELIM and 11.5/ 12.4 months in FIRE-3-LLD in either treatment arm. In the LICC trial, median overall survival (mOS) in secondarily resected pts was 65.1 months, with 38.3 months for the R1 and is not yet reached for the R0 subgroup. In CELIM, mOS was 53.9 months for R0 resected pts. In FIRE-3-LLD, after secondary resection mOS was 56.2 months. Median age was about 5 years less in LICC. Further details will be presented. Conclusions: Secondary resected pts of LICC, CELIM and FIRE-3 showed impressive median OS with better OS for LICC and a younger patient cohort. The established tight LICC surveillance program after surgery might have had a positive impact on survival. Clinical trial information: LICC: NCT01462513; FIRE-3: NCT00433927; CELIM: NCT00153998.

Markers of metastatic colorectal cancer.

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death. However, early diagnosis of CRC metastases offers a chance of long-term survival in as much as 40% of patients after curative treatment. Current guidelines are based on clinical examination, carcinoembryonic antigen (CEA) testing, computed tomography scanning, and endoscopic surveillance. Although CEA is the most widely used laboratory test, it has very low sensitivity (30–40%). Moreover, there is no evidence to support the association of CEA testing with improved survival or quality of life. Thus, novel markers with greater specificity and sensitivity are needed. The aim of this review was to define the role of available laboratory markers in early diagnosis of metastatic CRC. We identified novel tests with the highest association to metastatic CRC: circulating tumour DNA, growth/differentiation factor 15, and β6-integrin. We also discuss other promising markers, although most of the studies are preliminary and require validation.

ECCO2R as a bridge to a decision in type II respiratory failure.

End-of-life decisions are often time consuming and difficult for everyone involved. In some of these cases extracorporeal life support systems could potentially be used not only as a bridge to treatment but as a tool to buy time to allow patient's participation in decision making and to avoid further futile invasive procedures. A previously healthy 53-year-old female patient presented with respiratory failure of unknown cause. In the course of treatment her condition was deemed irreversible and the only option for any chance of long-term survival was a lung transplant. During this whole time the patient's condition was managed with extracorporeal carbon dioxide removal system (ECCO2R). She remained compos mentis and expressed the wish to stop all the treatment as the option of lung transplant was not acceptable to her. Treatment was withdrawn and she passed away. In cases of end-of-life decisions, time can play an essential role. Even though extracorporeal life support systems have been conceptualised to be a bridge to treatment, they could be beneficial in a situation when time is needed to make a decision. ECCO2R has been used as a treatment method in different settings, however, in this case it served as a tool to maintain the patient alive and conscious for a sufficient time for her to participate in decision making. Our case report demonstrated that ECCO2R could serve as a bridge to decision in situations when time is limited and the decisions that need to be made are difficult.

Universal screening of newborns for biliary atresia: Cost-effectiveness of alternative strategies.

Objective Biliary atresia, a rare newborn liver disease, is the most common cause of liver-related death in children and the main indication for paediatric liver transplantation. Early detection and surgical intervention with a Kasai portoenterostomy offers the best chance for long-term patient survival. We conducted a cost-effectiveness analysis to compare no universal screening with screening using either a home-based infant stool colour card with passive card distribution strategy, or conjugated bilirubin testing. Methods A Markov model was developed, with structure, costs, and probabilities informed by the literature and clinical expert opinion, to simulate a newborn cohort over a 10-year time horizon. Health benefits were expressed as life-years gained. This analysis was conducted from the perspective of the Canadian publicly funded health care system (all costs in Canadian dollars). Both deterministic and probabilistic analyses were conducted. Results Screening using a home-based colour card with passive card distribution was a cost-effective option. For a population of 392,902 annual births in Canada, this strategy cost approximately $192,000 more than no universal screening but led to eight life-years gained (incremental cost-effectiveness ratio (ICER) = $24,065 per life-year gained). Screening using conjugated bilirubin testing versus the colour card cost $2,369,199 more and led to five more life-years gained (ICER= $473,840 per life year gained), and so was not cost-effective. Conclusions A home-based screening program using infant stool colour cards with a passive distribution strategy could be highly cost-effective when administered at a low unit cost and with a reasonable screening performance.

AB010. S2-4. Hepatopancreatoduodenectomy (HPD) for cholangiocarcinoma

: Major hepatectomy combined with pancreatoduodenectomy [hepatopancreatoduodenectomy (HPD)], is indicated for laterally advanced cholangiocarcinoma. Since Takasaki et al. first introduced HPD for the treatment of locally advanced gallbladder cancer in 1980, many Japanese surgeons and a small number of Western surgeons have employed this extended procedure for the treatment of biliary cancer. However, limited number of patients and high rate of mortality hindered our ability to reach to definitive conclusion regarding the survival benefit of this procedure. Even today, HPD for biliary cancer remains controversial and is the most challenging operation. In 2012, we reported the surgical outcome of 85 patients with cholangiocarcinoma who underwent HPD. The main tumor location was perihilar in 59 patients and distal in 26 patients. The types of hepatectomy performed included right-sided hepatectomy in 55 patients, left-sided hepatectomy in 23 patients, and central hepatectomy in 7 patients. Combined portal vein resection was performed in 24 patients, and hepatic artery resection was performed in 7 patients. Despite this aggressiveness, mortality rate was only 2.4%, and overall 5-year survival rate was 37.4%. Survival rate of 57 patients with pM0 disease who underwent R0 resection was 54.3%. Our data demonstrate that HPD can be performed with low-mortality rate and offers improved chance of long-term survival in selected patients. We stress that HPD is an important procedure for treating extensively spreading cholangiocarcinoma that is otherwise unresectable, and it is now the fourth standard procedure following hepatectomy, bile duct resection, and pancreatoduodenectomy. The current challenge is super-extended resection, i.e., hepato-ligamento-pancreatoduodenectomy (HLPD), in which HPD is performed with an en bloc resection of the hepatoduodenal ligament requiring the simultaneous resection of the portal vein and hepatic artery. Till date, we have performed this super-extended surgery in 9 patients. I will mention its outcome in this lecture.

Disseminating laparoscopic skills for endometrial cancer

Introduction: Total hysterectomy with biltaeral salpingo-oopohorectomy offers the best chance of long term survival in endometrial cancer. Laparoscopic hysterectomy is associated with a lower incidence of postoperative complication and reduced hospital admission. In this district general hospital, the impression was that the rate of laparoscopic intervention was low with all total laparoscopic hysterectomies performed by one visiting gynae-oncological subspecialist.

SELDI-TOF MS Analysis of Hepatocellular Carcinoma in an Australian Cohort

BackgroundHepatocellular carcinoma (HCC) is a common cause of cancer death worldwide. Resection offers the best chance of long-term survival, but a consistent adverse prognostic factor is the presence of microvascular invasion (MVI). In this study, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), a high throughput method of analyzing complex samples, was used to explore differentially expressed proteins between HCC and adjacent nontumour liver tissue (ANLT). These findings were correlated with clinical outcomes. Materials and methodsFrom 2002 to 2011, tumor and ANLT were collected from patients who underwent liver resection and these samples were later prepared for SELDI-TOF MS. Output data were then used to identify proteins capable of discriminating HCC from ANLT. Proteins from the multivariate analysis were then analyzed to determine prognostic factors and the m/z ratios of these proteins were entered into the ExPASy database to infer potential candidates. ResultsDuring the study period, 30 patients had SELDI-TOF MS performed on their HCC and ANLT samples. On multivariate analysis, a panel of four proteins—m/z 5840, m/z 8921, m/z 9961, and m/z 25,872—discriminated HCC from ANLT with an area under the ROC curve of 0.954 (P < 0.001). On prognostic factor assessment, decreased m/z 9961 was significantly associated with the presence of MVI (P = 0.025) and shorter disease-free survival (P = 0.045) in our patients. A potential candidate for this protein was coxsackievirus and adenovirus receptor, isoform 3 (CAR 3/7), which helps maintain tight junction integrity. ConclusionsUsing SELDI TOF-MS, we identified a panel of four proteins with excellent discriminative capacity between HCC and ANLT. Of these, m/z 9961 was the only protein significantly associated with a known poor prognostic factor (presence of MVI) and survival (shorter disease-free survival). While loss of CAR 3/7 could lead to MVI, further research is warranted to validate the identity of protein m/z 9961.

Survival after secondary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (CELIM, FIRE-3).

571 Background: Metastatic colorectal cancer (mCRC) patients (pts) with liver-limited disease (LLD) have a chance of long-term overall survival (OS) and potential cure after complete hepatic metastasectomy. The appropriate postoperative treatment strategy is still controversial. L-BLP25 as antigen-specific cancer vaccine targeting mucin 1 (MUC1) was recently evaluated as adjuvant therapy in mCRC pts after R0/R1 LLD resection (LICC trial, NCT01462513). Here we compared the LICC surveillance program and efficacy results for secondarily resected LLD pts versus historical controls, i.e. the CELIM trial (Folprecht et al, Ann Oncol 2014) of potentially resectable LLD mCRC pts and a FIRE-3-LLD subgroup (Holch et al, Int J Cancer 2018). Methods: LICC, CELIM and FIRE-3-LLD subgroup pts with stage IV mCRC limited to liver metastases who underwent hepatic resection (R0 or R1) were compared regarding pts characteristics, surveillance and efficacy outcome. LICC pts received adjuvant L-BLP25 or placebo after secondary LLD resection as 8 weekly doses, followed by 6 week maintenance intervals and tight surveillance until recurrence or a maximum of 2 years. Results: In LICC, 41/121 pts (33.9%) were secondarily resected, and R0 resection was achieved in 31 pts (75.6%). In CELIM, 36/106 pts (34%) with primary unresectable LLD were secondarily R0 resected. In FIRE-3-LLD, secondary resection was feasible for 29/133 pts (21.8%). After R0 resection, median recurrence free survival (mRFS) was 8.9 months in LICC, 9.9 months in CELIM and 11.5/12.4 months in FIRE-3-LLD in either treatment arm. In the LICC trial, median overall survival (mOS) in secondarily resected pts was 65.1 months, with 38.3 months for the R1 and is not yet reached for the R0 subgroup. In CELIM, mOS was 53.9 months for R0 resected pts. In FIRE-3-LLD, after secondary resection mOS was 56.2 months. Median age was about 5 years less in LICC. Further details will be presented. Conclusions: Secondary resected pts of LICC, CELIM and FIRE-3 showed impressive median OS with better OS for LICC and a younger patient cohort. The established tight LICC surveillance program after surgery might have had a positive impact on survival. Clinical trial information: LICC: NCT01462513; FIRE-3: NCT00433927; CELIM: NCT00153998.

Feasibility of cytoreductive surgery and intraperitoneal chemotherapy for pseudomyxoma peritonei in a rural hospital in India

Background: Cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy provides the only chance for long-term survival for selected patients diagnosed with a variety of peritoneal neoplasm, either primary or secondary to digestive or gynecologic malignancies. Conventionally HIPEC (Hyperthermic Intraperitoneal Chemotherapy) is performed by open (Coliseum Technique) or closed method using a machine having roller pump and heat exchanger to maintain the flow of chemotherapy solution and it’s temperature (410-430C). The present article is about sharing our technique of delivering intraperitoneal chemotherapy and its outcome in a remote place in India where HIPEC machine is not available.

Evolutionary Rescue Through Partly Heritable Phenotypic Variability.

Environmental variation is commonplace, but unpredictable. Populations that encounter a deleterious environment can sometimes avoid extinction by rapid evolutionary adaptation. Phenotypic variability, whereby a single genotype can express multiple different phenotypes, might play an important role in rescuing such populations from extinction. This type of evolutionary bet-hedging need not confer a direct benefit to a single individual, but it may increase the chance of long-term survival of a lineage. Here, we develop a population genetic model to explore how partly heritable phenotypic variability influences the probability of evolutionary rescue and the mean duration of population persistence in changing environments. We find that the probability of population persistence depends nonmonotonically on the degree of phenotypic heritability between generations: some heritability can help avert extinction, but too much heritability removes any benefit of phenotypic variability. Partly heritable phenotypic variation is particularly advantageous when it extends the persistence time of a declining population and thereby increases the chance of rescue via beneficial mutations at linked loci. We discuss the implications of these results in the context of therapies designed to eradicate populations of pathogens or aberrant cellular lineages.

αβ T Cell-Depleted Haploidentical Hematopoietic Stem Cell Transplantation without Antithymocyte Globulin in Children with Chemorefractory Acute Myelogenous Leukemia.

We evaluated the outcome of αβ T cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory acute myelogenous leukemia (AML). Twenty-two patients with either primary refractory (n = 10) or relapsed refractory (n = 12) AML in active disease status received a transplant from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent myeloablative conditioning with treosulfan and thiotepa. Antithymocyte globulin was substituted with tocilizumab in all patients and also with abatacept in 10 patients. Grafts were peripheral blood stem cells engineered by αβ T cell and CD19 depletion. Post-transplantation prophylactic therapy included infusion of donor lymphocytes, composed of a CD45RA-depleted fraction with or without a hypomethylating agent. Complete remission was achieved in 21 patients (95%). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 18%, and the cumulative incidence of chronic GVHD was 23%. At 2 years, transplantation-related mortality was 9%, relapse rate was 42%, event-free survival was 49%, and overall survival was 53%. Our data suggest that αβ T cell-depleted haploidentical HSCT provides a reasonable chance of long-term survival in a cohort of children with chemorefractory AML and creates a solid basis for further improvement.

Surgical therapy of primary hepatic angiosarcoma

BackgroundPrimary hepatic angiosarcoma (PHA) is a rare tumor entity. Radical surgical resection is currently considered the best treatment choice. The aim of this analysis is to report our experience with surgery for PHA.MethodsAll resections of PHA from 01/2002 until 06/2017 were identified from our prospective institutional database. All cases were re-confirmed by a second pathologist. We analyzed completeness of resection, overall (OS) and disease-free survival (DFS).ResultsNine patients with PHA underwent hepatic resection. Median follow-up after surgery was 15.5 months (range: 3–144). At last follow-up 4/9 patients were alive, three of them without recurrence 15, 21 and 144 months after surgery. Five patients developed PHA recurrence. Four of these died 3 to 17 months after surgery. One patient with PHA recurrence is alive 15 months after surgery. Another patient without PHA recurrence died 59 months after surgery from pancreatic cancer. Median OS and DFS after resection was 18 months (range: 3–144 months) and 10 months (range: 2–144 months), respectively. After R-0 resection (n = 8), the median OS and DFS was 59 and 11 months.ConclusionsResection of PHA is the only approach to achieve complete tumor removal and offers a chance for long-term survival and should be evaluated in cases of PHA.

Portal vein resection during pancreatic resection for inflammation instead of true tumor infiltration – A false positive benefit for overall survival?

Background: Extended pancreatic resections including resections of the portal (PV) may nowadays be performed safely. Limitations in distinguishing true tumor involvement from inflammatory adhesions however result in PV resections being performed without histological evidence of tumor infiltration. The aim of this study was to analyze the impact of these false positive resections on operative outcome and long-term survival. Methods: 40 patients who underwent pancreatic resection with PV resection for pancreatic adenocarcinoma (PA) without tumor infiltration of the PV (PVR-group) were identified. In a 1:3 match these patients were compared to 120 patients who underwent standard pancreatic resection without PV resection (PD-group) with regard to operative outcome and overall survival. Results: A pancreatic head resection was performed in 63% of the patients whereas 37% underwent a total pancreaticoduodenectomy. Overall postoperative complications > Clavien II were observed in 14 patients (35%) of the PVR group and 19 patients (16%) of the PD group (p = 0.01). Postoperative mortality occurred in 2 patients (5%) of the PVR group vs. 1 patient (1%) of the PD group (p = 0.10). Overall survival was significantly decreased in the PVR group (p = 0.00). Conclusion: Radical resection affords the best chance for long-term survival in patients with PA. Based on the results of this study a routine resection of the PV as recently proposed may however not be recommended.

Gallbladder Adenosquamous Carcinoma Associated with Biliopancreatic Maljunction: aggressive resection and survival

Background: Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join outside the duodenal wall. It has been reported to be associated with an increased risk of gallbladder carcinoma. Gallbladder adenosquamous carcinoma is rare, with a worse prognosis compared to patients with adenocarcinoma. We report a case of adenosquamous carcinoma of gallbladder associated with PBM. Methods: A 56-year-old woman was admitted to the hospital complaining of pain in right hypochondrium. Ultrasonography and computed tomography revealed an elevated lesion inside the gallbladder and dilated extrahepatic bile duct. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed PBM with biliary dilatation of 15mm in the largest diameter. Results: Cholecystectomy, bile duct resection with a Roux-en-Y hepaticojejunostomy and hepatic resection (S4b-S5) with regional lymphadenectomy was performed. Histology demonstrated an adenosquamous cell carcinoma of the gallbladder with invasion to the muscle layer and two metastases of the resected lymph nodes (T2N1M0). Fourteen months after the operation, the patient is doing well with no signs of recurrence. Conclusion: PBM is a high risk factor for the development of gallbladder carcinoma because of a continuous reflux of pancreatic juice into the biliary tract. Aggressive surgical resection without residual tumor (R0) provides a chance for long-term survival in patients with gallbladder adenosquamous carcinoma.

High Expression of PQBP1 and Low Expression of PCK2 are Associated with Metastasis and Recurrence of Osteosarcoma and Unfavorable Survival Outcomes of the Patients.

Osteosarcoma (OS) is the most common primary bone malignancy, predominately affecting children and adolescents. Due to the introduction of chemotherapy, the 5-year survival rate of OS patients has dramatically improved to 60-70%. Unfortunately, OS patients with recurrence or metastatic disease have less than a 20% chance of long-term survival, despite aggressive therapies. In this study, we aimed to identify gene expression patterns associated with metastasis and recurrence in order to identify potential biomarkers with prognostic power. We found that high expression of polyglutamine tract-binding protein 1 (PQBP1) and low expression of phosphoenolpyruvate carboxykinase 2 (PCK2) were related to a high probability of recurrence and metastasis in OS patients and also predicted shorter recurrence-free survival (RFS) and metastasis-free survival (MFS) after adjustment for other clinical variables. Prediction models based on the combination of PQBP1 and PCK2 expression had good and robust predictive power for recurrence and metastasis. A PQBP1 and PCK2-centered protein interaction network was built, and the hypothetical regulatory path between them was identified and termed the PQBP1-SF3A2-UBA52-PCK2 axis. Gene enrichment analysis indicated that aberrations of metabolism might play an important role in recurrence and metastasis in OS patients. Accordingly, PQBP1 and PCK2 are crucial for recurrence and metastasis in OS, and these findings provide a molecular basis for the exploitation of diagnostic and therapeutic strategies for overcoming recurrence and metastasis in OS.

Caudate Lobectomy for Perihilar Cholangiocarcinoma - Current Evidence.

At the moment, surgery is considered the only therapeutic approach offering a chance of long-term survival in patients diagnosed with perihilar cholangiocarcinoma (PHC). Curative intent surgery for PHC has experienced significant technical improvements over the years, from simple bile duct resection to complex surgical procedures including lymph nodes dissection, major hepatectomies and, sometimes, vascular resections. The modern surgical approach of PHC is associated with significantly improved survival rates, albeit with increased postoperative morbidity. The initial Western experience with major hepatectomies for PHC was not encouraging, as it was associated with unacceptably high mortality rates. Currently the mortality rates after surgery for PHC have significantly decreased, but it appears that the mortality rates in Western centres still remain higher, compared with the East Asian centres. The differences of outcomes between East Asian and Western centres are explained not only by the management of PHC but also by patient characteristics. En bloc caudate lobectomy as part of radical resections for PHC has been reported in clinical practice nearly three decades ago. The rationale of en bloc caudate lobectomy is based on the pattern of tumour spread in PHC, taking in consideration the fact that caudate lobe invasion appears to be a frequent event in patients resected for PHC. While en bloc caudate lobectomy in the context of curative intent surgery for PHC has been discussed in a host of publications so far, the currently available literature reached conflicting results regarding its overall impact on the patient. Therefore, the aim of this paper is to review the current relevant literature pertaining to the impact of en bloc caudate lobectomy in the context of curative intent surgery for PHC.

Precision Oncology in Surgery: Patient Selection for Operable Pancreatic Cancer.

Objective:We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection.Background:Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease.Method:In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram.Results:High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables.Conclusions:Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.

Decision irrationalities involving deadly risks

This article provides an experimental analysis of two-armed bandit problems that have a different structure in which the first unsuccessful outcome leads to termination of the game. It differs from a conventional two-armed bandit problem in that there is no opportunity to alter behavior after an unsuccessful outcome. Introducing the risk of death into a sequential decision problem alters the structure of the problem. Even though play ends after an unsuccessful outcome, Bayesian learning after successful outcomes has a potential function in this class of two-armed bandit problems. Increasing uncertainty boosts the chance of long-term survival since ambiguous probabilities of survival are increased more after each successful outcome. In the independent choice experiments, a slim majority of participants displayed a preference for greater risk ambiguity. Particularly in the interdependent choice experiments, participants were overly deterred by ambiguity. For both independent and interdependent choices, there were several dimensions on which participants displayed within session rationality. However, participants failed to learn and improve their strategy over a series of rounds, which is consistent with evidence of bounded rationality in other challenging games.